Evidence suggests a significant percentage of adolescent regular smokers are interested in trying to quit smoking and frequently make attempts to quit, yet are unsuccessful in maintaining abstinence on their own. Despite a genuine desire to quit on the part of many adolescents, there is an increasing incidence of smoking among older adolescents that runs counter to the overall trends of smoking reduction seen in the general population. Unfortunately, psychosocial and pharmacological smoking interventions have yet to indicate clear effectiveness with youth. Moreover, depression-related vulnerabilities, particularly currently elevated depressive symptoms, are highly comorbid with smoking behavior and dramatically reduce cessation rates. As a result, new approaches to smoking cessation are needed for adolescent smokers with currently elevated depressive symptoms. Behavioral activation (BA) is an approach that may be especially relevant for youth. BA has been shown to effectively treat those with depressive disorders through reduction of depressive symptoms by increasing contact with positive reinforcing events. In its application to smoking, BA is a practical, treatment approach based on reinforcement theory that helps individuals develop a more healthy and active lifestyle to simultaneously address depressive symptoms and quit smoking. In considering key theoretical aspects of BA and its basis in reinforcement theory, the construct of reward sensitivity is of great importance. Because reward sensitivity differs greatly across individuals and different stages of development, the current application will take a translational approach. Finally, despite a strong body of work supporting the use of BA with addictions in adults, developmental considerations are critical when applying adult derived-treatment models to adolescents. The objective of the proposed project is to develop a specialized behavioral activation treatment for smoking in youth ages 18-21 with elevated depressive symptoms (BATSY). The project will take place in two phases. In the first phase, we will utilize focus groups and pilot testing with 15 youth to develop the BATSY treatment protocol. In Phase II, we will conduct an open-label trial of BATSY plus nicotine replacement therapy with 30 youth. In the context of testing this newly developed BA treatment for adolescent smokers with elevated depressive symptoms, we will use sophisticated fMRI methodology to examine the extent to which baseline reward sensitivity is associated with treatment response. To achieve these multidisciplinary goals at the integration of neurodevelopmental and neurobehavioral methods with behavioral treatment development for adolescent smokers, in line with RFA-DA-10-003, we will establish a translational collaboration of researchers from University of Maryland, NIMH, and Yale University. PUBLIC HEALTH RELEVANCE: Adolescent smokers with elevated depressive symptoms are at significant risk to develop into chronic adult smokers, yet smoking treatments specifically targeted to their needs are absent. This application represents the first effort to develop and test a specialized behavioral activation (BA) base protocol for this extremely at- risk group of youth using a translational, multidisciplinary team-building approach.